The lung is a surprisingly important target for the long term health effects of ingestion of inorganic arsenic in drinking water, but the impact of exposure during childhood is largely unknown. Children are likely to be especially susceptible since the development of the lung continues into childhood. In Chile, we have found that people who were exposed to arsenic in drinking water as children have 10-fold increased risks of lung cancer and chronic respiratory disease mortality when they become adults. In West Bengal, India we have found that adults with arsenic-caused skin lesions and high arsenic drinking water exposures have impaired lung function and increased rates of chronic respiratory disease. To date however, the impact of arsenic ingestion on lung function and respiratory health has not so far been studied in children. This application takes advantage of the fact that our collaborators in Bangladesh have examined 167,000 people for skin lesions and measured the arsenic concentrations in their drinking water. We plan to study 300 children aged 6-16 years living in the families having tube well water arsenic concentration mostly over 300 ug/L, and in which at least one member of the family has developed arsenic-related skin lesions. An unexposed comparison group of 300 children will be selected from families with no skin lesions, and whose water contains less than 50 ug/L. Lung function and respiratory symptoms, including chronic cough and shortness of breath, will be assessed in relation to current and past arsenic concentrations in all sources of drinking water throughout childhood, including in utero exposure. Potential susceptibility and interactions associated with indoor air pollution, diet, and nutritional status, will be investigated. Differences in susceptibility due to individual variability in the degree to which children metabolize arsenic to highly toxic methylated compounds identified in urine samples will also be assessed. The children in these exposed and unexposed families provide a unique opportunity to identify the effects of arsenic exposure during critical time periods of lung growth and development. The public health impact of adverse respiratory effects due to arsenic exposure in early life could be substantial given the large number of children exposed to arsenic in drinking water worldwide and the relevance of these outcomes for future population morbidity and mortality.